The Stories of the Scientists Behind Immuno-Oncology, in Their Own Words

Dec 21, 2017

ASCO Members Profiled in A Cure Within

CTLA-4James Allison, PhD
Memorial Sloan Kettering Cancer Center

Jedd Wolchok, MD, PhD
Memorial Sloan Kettering Cancer Center

Axel Hoos, MD, PhD
GlaxoSmithKline

PD-L1Gordon Freeman, PhD
Dana-Farber Cancer Institute

Suzanne Topalian, MD
Johns Hopkins University

VaccinesDrew Pardoll, MD, PhD
Johns Hopkins Medicine

Elizabeth Jaffee, MD
Johns Hopkins Medicine

IL-2Steven Rosenberg, MD, PhD
National Cancer Institute

CAR-TPatrick Hwu, MD
MD Anderson Cancer Center

Carl June, MD
Perelman School of Medicine at the University of Pennsylvania

Michel Sadelain, MD, PhD
Memorial Sloan Kettering Cancer Center

OncolyticsRobert Coffin
Replimune

STINGTom Gajewski, MD, PhD
University of Chicago

MicrobiomeLaurence Zitvogel, MD
Gustav Roussy

By Kate MacDougall

As the world of immuno-oncology continues to expand rapidly, and as more and more immunotherapies are developed to improve the lives of those with cancer, a new book chronicles the contributions of the field’s pioneers—in their own words and drawings.

A Cure Within: Scientists Unleashing the Immune System to Kill Cancer profiles 25 oncologists and scientists, including 14 ASCO members. Each section focuses on a different element of immuno-oncology—including CAR-T, vaccines, PD-L1, and CTLA-4—and each chapter takes a deep dive into the work of the major players responsible for bringing these innovations to life.

But instead of relaying history or detailing the science behind each of these discoveries, A Cure Within tells the story behind the story, from the pioneering scientist’s point of view.

“We live in an age where science isn’t popular, and, therefore, most people have never met a scientist firsthand,” said author Neil Canavan. “I want people to know about this extraordinary immuno-oncology revolution that’s happening and to show how the people involved are normal and accessible.”

Through his work as scientific advisor for The Trout Group, a life sciences investor relations firm, Mr. Canavan became interested in immuno-oncology and began seeking out those in the field to learn more. After framing and hanging in his office an impromptu scientific sketch he commissioned from famed Israeli immunologist Zelig Eshhar, PhD, other oncologists and scientists began asking Mr. Canavan if they could add to his collection.

“The head of immunotherapy at Johns Hopkins, Drew Pardoll, came into my office, pointed to [Dr. Eshhar’s] drawing on my desk, and said, ‘That guy’s really famous! Can I do one?’” explained Mr. Canavan. “And it kept going like that until I had about 40 drawings of various aspects of immuno-oncology.”

The book showcases 23 of these drawings, each connected to a specific scientist’s chapter, which can be read individually or all together in any order.

The ‘Wacky Idea’ of CAR T-Cell Therapy

One chapter in the chimeric antigen receptor (CAR) T-cell section tells the story of how Michel Sadelain, MD, PhD, director of the Center for Cell Engineering & Gene Transfer and Gene Expression Laboratory at Memorial Sloan Kettering Cancer Center (MSKCC), faced skepticism, failure, and just plain weird looks as he pressed on with his “wacky idea” of inserting genes into T cells.

“Often, when [my group] was invited to meetings in the early days, we tended to be scheduled on the last day at the last session when everybody is checking out of the hotel; that’s where you would have the session on T-cell engineering,” Dr. Sadelain said. “Since then, we’ve learned that T cells are the centerpiece of all immunotherapy, but they often need some help. We work to enhance T cells through genetic engineering.”

Dr. Sadelain’s perseverance is now paying off, big time. Two CAR-T cell therapies were recently FDA approved for the treatment of hematologic cancers—with a third approval close on their heels.

“The signaling properties of these [newly approved] CARs were designed in 2002 and 2004,” Dr. Sadelain said. “Needless to say, progress has been made since then, and we can anticipate continuing improvements in their design.”

Scientists are already looking beyond these newly approved treatments, what Dr. Sadelain calls “second-generation CARs,” addressing their toxicities and relapse rates, and exploring their use in the world of solid tumors.

He said that his accompanying drawing—entitled “CAR T-cell in Action”—came about after Mr. Canavan “handed me a pad of paper after one of my talks and asked me to make a drawing of what I do.” Dr. Sadelain aptly chose to depict the process to which he has devoted his career.

The Development of Ipilimumab (and Music)

In other chapters and drawings from A Cure Within, we learn something about the personal life of the scientist. Many of the pioneers profiled discuss their love of music and how it intersects with their work, like Tom Gajewski, MD, PhD, James Allison, PhD, and Patrick Hwu, MD, who make up part of the rock and blues band The CheckPoints, consisting entirely of immunotherapy oncologists and researchers.

The drawing by Jedd Wolchok, MD, PhD, chief of the Melanoma and Immunotherapeutics Service at MSKCC, also showcases his passion for music—in particular, the tuba. A string of music notes can be seen across the top of his illustration, which also depicts the immunotherapy that he played a major role in bringing to approval: ipilimumab.

“[My illustration] outlines that immunotherapies like ipilimumab are more directed at the patient than they are at the tumor,” he said. “The less like ‘self’ the tumor appears to the immune system, the more likely the immune system will see it as something worthy of its attention.”

The chapter featuring Dr. Wolchok, within the CTLA-4 section, details his work with Dr. Allison—storied immunologist and harmonica player for The CheckPoints, also profiled in the book—to hone the landmark CTLA-4-blocking antibody ipilimumab for melanoma treatment. The story starts, however, back in high school, when Dr. Wolchok spent a summer working in an immunology lab, and goes on to show the optimism he’s maintained about this field of science throughout his career.

“I feel grateful for the opportunity to have witnessed the rise of immuno-oncology, and to be able to have a very different conversation with patients now compared with conversations I had 5 or 10 years ago about the potential outcomes from their illness,” Dr. Wolchok said. “But it’s also humbling to see that not everybody benefits in a durable way and that more work is necessary.”

Since 2009, Dr. Wolchok and his team have also pushed for the regulatory use of treatment response criteria that take into account the slower response time and other differences between immunotherapies and standard anticancer therapies.

“This is a new way to think about judging the activity of anticancer therapies that takes into consideration some of the unique biology that comes with manipulating the immune system, rather than focusing on treating the tumor directly,” he explained.

Looking onward, Dr. Wolchok has high hopes for the field of immuno-oncology, including the potential for combining immunotherapies with other immunotherapies and with other anticancer agents to create even more therapeutic options for patients.

“The field should lead us to a point where we have a data-driven treatment plan for every patient that results in elimination of the disease or at least durable control—changing it from a cause of death to something that a patient can comfortably live their life with and be treated for as needed,” he said.

Supporting Future Immuno-Oncology Pioneers

In an effort to further the field of immuno-oncology and cultivate future pioneers like those profiled in A Cure Within, the book’s publisher, Cold Spring Harbor Press, is donating all publishing proceeds to cancer research in its Cold Springs Labs. Mr. Canavan is also donating all author royalties from the book’s first year to the Cancer Research Institute, the founding society for immuno-oncology research.

“The stories and lives shared in this book show readers the decades of devotion and passion it takes to imagine a better world and then make it happen,” said ASCO CEO Clifford A. Hudis, MD, FACP, FASCO. “If this book motivates even one more similarly talented and visionary investigator to deliver on their promise it would be a wonderful success.”